Background Airway epithelial cells (AEC) are quite difficult to access in newborns and infants. It is critically important to develop robust life-extended models to conduct translational studies in this age group. We propose the use of a recently described cell-culture technology (conditionally reprogrammed cells - CRC) to generate continuous primary cell cultures from nasal and bronchial AEC of young children. Methods We collected nasal and/or bronchial AEC from a total of 23 subjects of different ages including newborns/infants/toddlers (0–2 years; N=9), school age children (4–11 years; N=6), and a group of adolescent/adult donors (N=8). For CRC generation, we used conditioned medium from mitotically inactivated 3T3 fibroblasts and Rho-associated kinase (ROCK) inhibitor (Y-27632). Antiviral immune responses were studied using 25 key antiviral genes and protein production of type III epithelial interferon (IFN λ1) after double stranded (ds) RNA exposure. Results CRC derived from primary AEC of neonates/infants and young children exhibited: 1) augmented proliferative capacity and life-extension, 2) preserved airway epithelial phenotype after multiple passages, 3) robust immune responses characterized by expression of innate antiviral genes and parallel nasal/bronchial production of IFN λ1 after exposure to dsRNA, and 4) induction of airway epithelial inflammatory and remodeling responses to dsRNA (e.g. CXCL8 and MMP9). Conclusion Conditional reprogramming of AEC from young children is a feasible and powerful translational approach to investigate early-life airway epithelial immune responses in humans.

Asthma is the most common chronic disease of childhood in the United States, affecting more than 4 million (6%) children under the age of 18 years. 1 Multiple factors contribute to asthma symptoms, diagnosis and morbidity including indoor air pollutants. 2 More than

Purpose of reviewAsthma is the most common chronic disease of childhood. Environmental exposures, such as allergens and pollutants, are ubiquitous factors associated with asthma development and asthma morbidity. In this review, we highlight the most recent studies relevant to childhood asthma risk, onset, and exacerbation related to air pollution exposure.Recent findingsIn this article, we review current research that has been published between 2021 and 2022, demonstrating the effects of early-life exposure to key air pollutants (e.g., particulate matter (PM), nitrogen dioxide (NO2), sulfur dioxide (SO2) and ground-level ozone (O3), environmental tobacco smoke, radon, and volatile organic compounds (VOC) on respiratory health.SummaryAir pollution continues to be a global burden with serious consequences related to respiratory health. Interventions aimed at reducing air pollution in the environment must be achieved in an effort to improve asthma outcomes and pediatric health.